Intracellular lipid accumulation is an important process characteristic of many pathological conditions. Both the causes and the effects of intracellular lipids have been investigated for many years, but the roles of the complex and multiple factors remain controversial, partly because of the difficulties of working with whole animal or organ models. It is the purpose of this project to investigate the causes and effects of lipid accumulation with the use of a relatively simple controlled system. Isolated mammalian cells are used and exposed to test media with known lipid compositions. Combined ultrastructrual, histochemical and biochemical procedures are employed in order to correlate lipid accumulation with structural alterations and functional abnormalities. Cellular injuries including hypoxia, specific metabolic inhibitors, drugs and agents that increase membrane permeability are being studied to determine their effect on the uptake and accumulation of the different forms of lipid used in the experimental system. Various injuries will be combined in order to study additive effects on lipid deposition. Modifications in the environment that tend to limit or reverse lipid accumulation will be examined. The previously noted striking toxic effects of long-chain saturated, as opposed to unsaturated, fats, on cell structure, and function will be further pursued. The basic objective of this research is to increase our understanding of the pathogenesis and injurious effects of lipid deposition, so that scientific approaches toward control of this process could be developed that would have eventual clinical significance in lipid accumulative disorders such as atherosclerosis.